Schizophrenia Bulletin Advance Access originally published online on March 28, 2008
Schizophrenia Bulletin 2008 34(3):419-422; doi:10.1093/schbul/sbn015
© The Author 2008. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.
Paliperidone for Treatment of Schizophrenia
Abraham M. Nussbaum1,2 and
T. Scott Stroup2
2 Department of Psychiatry, University of North Carolina Hospitals, Campus Box No. 7160, Chapel Hill, NC 27599-7160
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Abstract
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In short-term studies, oral paliperidone is an antipsychotic
that is more efficacious than placebo. We found its adverse
effects to be similar to those of its parent compound, risperidone,
with movement disorders, weight gain, and tachycardia all more
common with paliperidone than placebo. In addition, paliperidone
is associated with substantial increases in serum prolactin
that may be associated with sexual dysfunction, although sexual
functioning outcomes were not reported. At doses greater than
3 mg per day, oral paliperidone appears comparable in efficacy
to oral olanzapine 10 mg per day. Regarding the critical comparison
of oral paliperidone to risperidone, we have no information
and are thus unable to determine if paliperidone has any advantages
or disadvantages compared to its well-known parent compound.
Keywords: schizophrenia / paliperidone / systematic review / meta-analysis
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Background
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Paliperidone, 9-hydroxy-risperidone, is an active metabolite
of risperidone that is now commercially available in an oral
formulation. A long-acting intramuscular formulation may be
commercially available soon.
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Objectives
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To compare the effects of paliperidone with any other treatment,
including placebo, for people with schizophrenia and schizophrenia-like
illnesses.
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Search Strategy
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We searched the Cochrane Schizophrenia Group's Register (December
2006) and inspected references of identified studies for further
trials. We contacted the manufacturers of paliperidone, the
Food and Drug Administration, and authors of relevant trials
for additional material.
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Selection Criteria
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We included all randomized clinical trials (RCTs) comparing
paliperidone to any treatment for schizophrenia and schizophrenia-like
illnesses.
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Data Collection and Analysis
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We independently selected and critically appraised studies,
extracted data, and analyzed on an intention-to-treat basis.
Where possible and appropriate, we calculated risk ratios (RRs)
and their 95% confidence intervals (CIs) with the number needed
to treat/harm (NNT/NNH). We calculated weighted mean differences
(WMDs) for continuous data.
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Results
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Five studies compared paliperidone with placebo. Fewer people
left the studies early if they were randomized to paliperidone
as shown in
Figure 1 (
n = 1647, 5 RCTs, RR = 0.68, CI = 0.61
to 0.76; NNT = 7, CI = 6 to 9), and those receiving any dose
of paliperidone were significantly more likely to have an improvement
in global state as indicated by at least 30% improvement in
Positive and Negative Syndrome Scale total score (
n = 1420,
4 RCTs, RR = 0.69, CI = 0.63 to 0.75; NNT = 5, CI = 4 to 6).
People randomized to paliperidone were less likely to experience
a recurrence (
n = 1638, 5 RCTs, RR = 0.45, CI = 0.31 to 0.66;
NNT = 16, CI = 13 to 26) than those allocated to placebo. Adverse
effect data were not well reported, but paliperidone does seem
to produce a greater incidence of tachycardia than placebo (
n = 1638, 5 RCTs, RR = 1.88, CI = 1.28 to 2.76; NNH = 21, CI =
11 to 90), and a consistent, significant elevation in serum
prolactin was found for both men (
n = 413, 3 RCTs, WMD = 27.68,
CI = 23.66 to 31.69) and women (
n = 252, 3 RCTs, WMD = 87.39,
CI = 74.27 to 100.51). People receiving paliperidone were more
likely to experience extrapyramidal disorders (
n = 1638, 5 RCTs,
RR = 2.21, CI = 1.26 to 3.88; NNH = 28, CI = 12 to 129) and
weight gain (
n = 769, 4 RCTs, WMD = 1.07, CI = 0.65 to 1.49).
In our sensitivity analyses examining dose, the results for
leaving the study early for any reason were favorable for all
specific doses of paliperidone.
Three studies compared various doses of paliperidone with olanzapine
10 mg daily. We found no differences between paliperidone and
olanzapine for leaving the study early as shown in
Figure 2 (
n = 1332, 3 RCTs, RR = 1.04, CI = 0.89 to 1.21; ca. 40% in
both groups left by 6 weeks). Those receiving any dose of paliperidone
were no more likely to have a recurrence of psychotic symptoms
than those receiving olanzapine 10 mg daily (
n = 1327, 3 RCTs,
RR = 1.07, CI = 0.64 to 1.76). People who received paliperidone
experienced less weight gain than those who received olanzapine
(
n = 660, 3 RCTs, WMD = –0.88, CI = –1.38 to –0.37).
Results for various movement disorders all favored olanzapine
(extrapyramidal disorder:
n = 1327, 3 RCTs, RR 2.99 CI 1.44
to 6.18; hyperkinesias:
n = 1327, 3 RCTs, RR 3.14 CI 1.53 to
6.42; and hypertonia:
n = 836, 2 RCTs, RR 9.28 CI 1.26 to 68.5).
In our sensitivity analyses examining dose, those randomized
to paliperidone 3 mg daily were more likely to leave early (
n = 255, 1 RCT, RR = 1.44, CI = 1.04 to 1.98, NNH = 7) compared
with those randomized to olanzapine 10 mg daily. However, there
was no difference in numbers leaving early for 6 (
n = 473, 2
RCTs, RR = 1.05, CI = 0.86 to 1.28, NNH = 54), 9 (
n = 503, 2
RCTs, RR = 1.11, CI = 0.86 to 1.43, NNH = 25), 12 (
n = 480,
2 RCTs, RR = 0.89, CI = 0.72 to 1.11, NNT = 25), or 15 mg (
n = 243, 1 RCT, RR = 0.92, CI = 0.62 to 1.35, NNT = 34).
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Implications for Practice
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Oral paliperidone is an effective antipsychotic whose optimal
dose appears to be between 6 and 12 mg per day, a dose range
in which its effectiveness is comparable to olanzapine 10 mg
per day. We found its adverse effects to be similar to those
of its parent compound, risperidone, with higher doses more
likely to cause movement disorders than lower doses. We observed
that people who received paliperidone 3, 6, or 9 mg per day
experienced less weight gain than those receiving olanzapine
10 mg per day, but found no difference for people receiving
paliperidone 12 or 15 mg per day. People who received paliperidone
9, 12, or 15 mg per day experienced more movement disorders
than those who received olanzapine 10 mg per day, but we identified
no difference for those receiving paliperidone 3 or 6 mg per
day. Paliperidone is associated with substantial increases in
serum prolactin in men and women, with larger effects in women
than men; the incidence of amenorrhea, anorgasmia, erectile
dysfunction, galactorrhea, and other sexual dysfunction, were
not reported in these studies.
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Implications for Research
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While no direct comparisons with its parent molecule risperidone
are available, we suspect that oral paliperidone will affect
people with schizophrenia in a similar fashion to risperidone.
For individual clinicians to select paliperidone over risperidone
on the basis of appropriate evidence, researchers will need
to conduct pragmatic studies that more closely resemble the
lived experience of patients with schizophrenia and include
comparisons with risperidone. Clinicians would also benefit
from studies that assess the efficacy, adverse effects, and
safety of long-term use of paliperidone, including behavior,
mortality, satisfaction with treatment, and cost-effectiveness
in comparisons to older and newer generation antipsychotics.
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Footnotes |
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1 To whom correspondence should be addressed; e-mail: tel: 919-966-8708 extension 5, fax: 919-966-9646, anussbau{at}unch.unc.edu.
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Acknowledgments
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The authors received no financial consideration from any parties
for the preparation of this review. Dr Stroup has been a consultant
for AstraZeneca, Janssen, Lilly, and Pfizer and has spoken at
events sponsored by Lilly, Lundbeck, and Pfizer.
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References
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- Nussbaum AM, Stroup S. Paliperidone for schizophrenia. Cochrane Database Syst Rev (2008) (Issue 2). In press.
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